Performance Characteristics for Physiological Measures of Progressive Pulmonary Fibrosis

Clinical measures of progressive pulmonary fibrosis (PPF) have been proposed, but their clinical utility remains unclear. To determine performance characteristics of lung function-based PPF measures, including new guideline criteria for discriminating clinically relevant outcomes. A multicenter retrospective cohort analysis was performed to assess the performance characteristics of eight categorical measures of forced vital capacity (FVC) and diffusion capacity (DLCO) decline, along with PPF guideline criteria (requiring two of the following: worsening respiratory symptoms, absolute decline in FVC ≥5% or DLCO ≥15%, or radiological progression) for discriminating two-year death or lung transplant among fibrotic ILD patients from the United States, United Kingdom and Canada (n=2727). The net benefit of the top performing measures to inform treatment initiation were compared using decision curves. PPF classified according to relative decline in FVC of 10%, relative decline in DLCO of 15% and PPF guideline criteria displayed best overall test performance, with area under the receiver operator curves of 0.67-0.68. Specificity was higher than sensitivity for all evaluated measures, with relative measures of lung function decline outperforming absolute measures. The net benefit of stand-alone relative decline in FVC ≥10% and DLCO ≥15% was similar to PPF guideline criteria across the range of treatment probability thresholds. Classifying PPF by stand-alone measures of FVC and DLCO decline provides similar clinical utility as PPF guideline criteria. Top performing physiology-based measures of PPF discriminate outcomes with high specificity, but low sensitivity.